POS0919 MOLECULAR AND BIOLOGICAL PATHWAYS OF BREAST CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS: IMMUNOHISTOCHEMICAL INVESTIGATIONS FROM THE SCLERO-BREAST STUDY
Authors: A. Spinella, A. Toss, C. Isca, M. De Pinto, C. Vacchi, L. Magnani, F. Lumetti, P. Macripo’, G. Ficarra, L. Fabbiani, A. Iannone, E. Gasparini, S. Piana, L. Cortesi, G. De Santis, A. Maiorana, M. Dominici, C. Salvarani, D. Giuggioli
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic Sclerosis (SSc) is a life-threatening connective tissue disease characterized by endothelial dysfunction, autoimmune abnormalities and aberrant fibrosis. Several reports showed an increased risk of cancer in SSc compared to general population, including breast cancer (BC). The relationship between BC and SSc has long been discussed with contradictory results. In our recent Sclero-Breast study we analyzed clinical-pathological features of BC in SSc; we finally observed the development of BC with early stages and good prognosis among these patients. Objectives The aim of this project was to explore the immunohistochemical (IHC) expression of potential biomarkers involved in the molecular pathways at the basis of SSc and BC etiophatogenesis as update analysis from the Sclero-Breast study. Methods Our observational multicenter retrospective study, performed at Modena University Hospital and Reggio Emilia Hospital in northern Italy, enrolled 33 SSc women with a personal history of BC between January 2017 and December 2019. Clinical and pathological characteristics of BC and SSc were collected. For 22 patients, BC tissues were available and IHC analysis was performed using specific antibodies to evaluate biomarkers and pathways potentially involved. The antibodies used included: PI3K/mTOR/TGFβ/PDGFRα/PDGFRβ/VEGF/EGFR/IL-6/CTLA-4/PDL1. We also reported TILs percentage (stromal tumor-infiltrating lymphocytes) of each sample. The following scores were assigned for general IHC analysis: (-) negative, (1+) positive tumor cells &lt;20%, (2+) positive tumor cells 20-50%, (3+) positive tumor cells &gt;50%. For PDL1 we considered a positivity in case of PD-L1 expression ≥1% in infiltrating inflammatory cells. For TILs quantification we applied the score: 0 (negative), ≤ 50% (low-median expression), &gt;50% (high expression). Results The first IHC analysis was performed on the samples of invasive BC patients (20 pts) and showed a prevalence of high PI3K expression (score of 3+ in 55% of cases) with mTOR overexpression in 45%. A PDL1 positivity was detected in 30%, with high TILs expression in 30%. Biopsies from the 2 pts with ductal carcinoma in situ were characterized by a negativity of almost all parameters, except for a medium-high TILs expression reported (40%/90% respectively). See Figure 1. IHC analysis was also performed according to BC subtypes. The group of HR+/HER2 negative showed high PI3K expression (score 3+) in most of cases (59%) with mTOR overexpression in 50%. CTLA-4 and PDL1 were positive in 25%, with high TILs expression in 25%. HER2 positive patients showed a high PI3K positivity in 50% of cases with mTOR positivity (score 3+) in 25% and high TGFβ expression (score 3+) in 25%. PDL1 was positive in 50% with high TILs expression in 25%. In Triple Negative group, PI3K overexpression was found in 75% of pts with half of cases represented by mTOR score 3+. PDL1 was positive in 50% with high TILs representation (80% of total cell count) in 50% of pts. Figure 1. IHC analysis and TILs% expression in histological samples of SSc patients with invasive BC. Conclusion According to our results, SSc patients with BC showed high positivity for PDL1 and high TILs representations in all subtypes. Furthermore, the high expression of PI3K, did not always correlate with mTOR overexpression. Further investigations on larger numbers are needed; however, these aspects seem to confirm that SSc subjects might develop BC at good prognosis, suggesting again a de-escalation strategy of cancer therapies. Finally, the possibility to personalize oncological targeted treatments in this subset of fragile patients could be promising. Disclosure of Interests None declared